This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term goal of our research program is to identify novel biomarkers of prostate cancer and to test their clinical utility either as diagnostic/prognostic factors, or as targets for therapeutic intervention. We thereby focus on the identification of biomarkers for both early as well as progressive disease. We have chosen an integrative approach employing human prostatic tissues of pre- and early malignant nature, as well as more defined cell models of prostate cancer progression. We will focus primarily on markers that can be detected in clinical laboratoried (for example proteins). We propose three progressive Specific Aims: First we will identify biomarkers in (i) epithelial and stromal cells derived from genetically modified tumor adjacent human prostatic tissues by generating proteomic expression profiles in comparison to disease-free prostatic tissues;and (ii) in an established cell model of prostate cancer progression. Second, using our collection of human prostatic tissues, we will validate potential biomarkers in tumor, matched tumor adjacent, and disease-free prostatic tissues. This analysis will allow us to determine the frequency, as well as cellular distribution of these biomarkers. The association of these parameters with clinical patient information will evaluate the marker's diagnostic/prognostic utility. Third, we will subject newly identified potential therapeutic targets to high throughput screening of small molecule inhibitors for the identification of lead drug compounds. These may lead to novel treatments in the preventive and/or adjunctive settting. This integrated approach is driven by an experienced team of biomedical researchers and an established network of trans-disciplinary collaborators.